Contributions
Abstract: S119
Type: Oral Presentation
Presentation during EHA23: On Friday, June 15, 2018 from 12:30 - 12:45
Location: Room A4
Background
The international AML relapse trial 2001/01 improved significantly the prognosis of children and adolescents with AML (Kaspers et al, JCO 2013). Since the end of recruitment in 2009, most relapsed AML have been enrolled to national or international registries, mainly continuing the established protocol.
Aims
This study analyses the outcome of children with relapsed and refractory AML between 2009 and 2016 (2009 Registry), including patients from Germany, Austria, Czech Republic, Switzerland, Poland, Italy Slovakia, Belgium and the Netherlands.
Methods
In total, 435 patients were enrolled, 395 with relapse and 43 with refractory disease. Children with acute promyelocytic leukemia and myeloid leukemia of Down Syndrome were excluded. For comparison, the updated AML-BFM and Dutch cohort out of the International AMLRelapse Trial 2001/01 was used (n=391; relapse n=351; refractory n=51). The recommended reinduction therapy was liposomal daunorubicin / fludarabine / cytarabine (L-DNR-FLA) followed by FLA course. Allogeneic stem cell transplantation (HSCT) was recommended in all patients.
Results
Most patients (89%) have been treated with the recommended re-induction therapy, however, due to the lack of L-DNR in some countries, idarubicin was used instead of L-DNR. In particular subgroups (mainly children with an early relapse), clofarabine (5%) or gemtuzumab ozogamicin (4%) containing regimens have been applied. The event-free (2nd EFS, 3 years) and overall survival (OS, 3 years) following relapse/ primary refractory AML were 42±2% and 51±3%, respectively. These data show a remarkable improvement in comparison to both 2nd EFS and OS of children enrolled in the International AML-Relapse Trial 2001/01 (2nd EFS 33±3%; OS 38±3%; p<0.005). Duration of first remission and genetic lesions remain significant prognostic factors: Remission <1 year vs >1 year: 2nd EFS: 32±3% vs. 57±4%; OS 36±3% vs. 60±4%; p< 0.00001; Core binding leukemia vs others: 2nd EFS: 57±4% vs. 31±3%; OS 61±4% vs. 37±3%; p< 0.0001. This improved outcome could be partially explained by an amelioration of the results obtained with alloSCT in 2nd CR or refractory disease (2nd CR: 2001/01 EFS 41±6% vs 2009 52±6%, p=0.07; refractory AML 19±7% vs 33±6%; p<0.003). In addition, 3rd line therapy including 2nd SCT (12%) was applied more often with a curative intention. The approaches to reinduce 3rd remission were heterogenous. They include both conventional chemotherapy schemes such as clofarabine/liposomal daunorubicin/ cytarabine as well as targeted treatment with gemtuzumab ozogamicin (GO) or other experimental approaches. Overall, the patients (n=53) who underwent 2nd SCT showed an EFS of 42± 7% (2001/01: 18±6%, p<0.001). Due to low number in subgroups and selection bias, no significant differences were found in terms of conditioning regimen or type of donor employed (BuCyMel, treosulfan/fludarabine; MSD, MUD, MMD, haplo).
Conclusion
Children with relapsed AML have a reasonable option to be cured with intensive 2nd and 3rd line therapy. Further research and trials are warranted to identify those children who will experience relapse earlier, for either apply more effective therapy or to for treating patients already when a molecular relapse will be detected. Prospective, randomized trials are urgently needed to identify the best conditioning regimen to be employed.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): AML, Children, Clinical Trial
Abstract: S119
Type: Oral Presentation
Presentation during EHA23: On Friday, June 15, 2018 from 12:30 - 12:45
Location: Room A4
Background
The international AML relapse trial 2001/01 improved significantly the prognosis of children and adolescents with AML (Kaspers et al, JCO 2013). Since the end of recruitment in 2009, most relapsed AML have been enrolled to national or international registries, mainly continuing the established protocol.
Aims
This study analyses the outcome of children with relapsed and refractory AML between 2009 and 2016 (2009 Registry), including patients from Germany, Austria, Czech Republic, Switzerland, Poland, Italy Slovakia, Belgium and the Netherlands.
Methods
In total, 435 patients were enrolled, 395 with relapse and 43 with refractory disease. Children with acute promyelocytic leukemia and myeloid leukemia of Down Syndrome were excluded. For comparison, the updated AML-BFM and Dutch cohort out of the International AMLRelapse Trial 2001/01 was used (n=391; relapse n=351; refractory n=51). The recommended reinduction therapy was liposomal daunorubicin / fludarabine / cytarabine (L-DNR-FLA) followed by FLA course. Allogeneic stem cell transplantation (HSCT) was recommended in all patients.
Results
Most patients (89%) have been treated with the recommended re-induction therapy, however, due to the lack of L-DNR in some countries, idarubicin was used instead of L-DNR. In particular subgroups (mainly children with an early relapse), clofarabine (5%) or gemtuzumab ozogamicin (4%) containing regimens have been applied. The event-free (2nd EFS, 3 years) and overall survival (OS, 3 years) following relapse/ primary refractory AML were 42±2% and 51±3%, respectively. These data show a remarkable improvement in comparison to both 2nd EFS and OS of children enrolled in the International AML-Relapse Trial 2001/01 (2nd EFS 33±3%; OS 38±3%; p<0.005). Duration of first remission and genetic lesions remain significant prognostic factors: Remission <1 year vs >1 year: 2nd EFS: 32±3% vs. 57±4%; OS 36±3% vs. 60±4%; p< 0.00001; Core binding leukemia vs others: 2nd EFS: 57±4% vs. 31±3%; OS 61±4% vs. 37±3%; p< 0.0001. This improved outcome could be partially explained by an amelioration of the results obtained with alloSCT in 2nd CR or refractory disease (2nd CR: 2001/01 EFS 41±6% vs 2009 52±6%, p=0.07; refractory AML 19±7% vs 33±6%; p<0.003). In addition, 3rd line therapy including 2nd SCT (12%) was applied more often with a curative intention. The approaches to reinduce 3rd remission were heterogenous. They include both conventional chemotherapy schemes such as clofarabine/liposomal daunorubicin/ cytarabine as well as targeted treatment with gemtuzumab ozogamicin (GO) or other experimental approaches. Overall, the patients (n=53) who underwent 2nd SCT showed an EFS of 42± 7% (2001/01: 18±6%, p<0.001). Due to low number in subgroups and selection bias, no significant differences were found in terms of conditioning regimen or type of donor employed (BuCyMel, treosulfan/fludarabine; MSD, MUD, MMD, haplo).
Conclusion
Children with relapsed AML have a reasonable option to be cured with intensive 2nd and 3rd line therapy. Further research and trials are warranted to identify those children who will experience relapse earlier, for either apply more effective therapy or to for treating patients already when a molecular relapse will be detected. Prospective, randomized trials are urgently needed to identify the best conditioning regimen to be employed.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): AML, Children, Clinical Trial